The sympathetic nervous system profoundly influences cardiovascular function. The sympathetic nervous system exerts its effects via the release of neurotransmitters and neuropeptides from postganglionic sympathetic neurons. Neuropeptide Y (NPY) is one such neuropeptide. In blood vessels, NPY is a constrictor and a mitogen for vascular smooth muscle (VSM). These actions of NPY affect normal cardiovascular function and have been implicated in the etiology of cardiovascular disease. The mechanisms regulating the synthesis and secretion of NPY from sympathetic neurons are not fully understood. Several lines of evidence suggest that targets of innervation modulate neuropeptide expression. This potential mechanism for regulation of NPY has not been studied in vascular sympathetic nerves. The experiments described in this proposal consider how interactions between vascular cells and postganglionic sympathetic neurons modulate neuronal expression of NPY. The overall hypothesis of the proposed studies is that vascular cells induce the expression of NPY in postganglionic sympathetic neurons. This hypothesis is tested in the first specific aim. Postgangliomc sympathetic neurons will be cultured in the presence and absence of vascular cells, and NPY mRNA and peptide expression measured. The second specific aim tests the hypothesis that vascular-derived nerve growth factor (NGF), transforming growth factor (TGF-f3), and/or vascular endothelial growth factor (VEGF) mediate or modulate the effects of vascular cells on sympathetic NPY expression. The effects of exogenous growth factors will be studied in neuronal cultures; the effects of vascular-derived growth factors will be studied in neuronal/vascular cocultures. The results of the proposed studies will indicate if vascular targets modulate the expression of NPY in sympathetic neurons, and if this modulation is dependent upon the actions of NGF, TGF-B and/or VEGF. The proposed studies will provide a greater understanding of how NPY is regulated in sympathetic neurons, and how the sympathetic nervous system, NPY, NGF, TGF-B and VEUF affect the physiological and pathological function of the cardiovascular system.